Improving dietary patterns in obese mice: Effects on body weight, adiposity, anhedonia-like behavior, pro-BDNF expression and 5-HT system.

INTRODUCTION: The excessive fat accumulation in obesity, resulting from an unbalanced diet, can lead to metabolic and neurological disorders and increase the risk of developing anxiety and depression. AIM: Assess the impact of dietary intervention (DI) on the serotonergic system, brain-derived neurotrophic factor (BDNF) expression and behaviors of obese mice. METHODS: Male C57BL/6 mice, 5 weeks old, received a high-fat diet (HFD) for 10 weeks for the induction of obesity. After this period, for 8 weeks, half of these animals received a control diet (CD), group obese (OB) + control diet (OB + CD, n = 10), and another half continued being fed HFD, group obese + HFD (OB + HFD, n = 10). At the end of the eighth week of intervention, behavioral tests were performed (sucrose preference test, open field, novel object recognition, elevated plus maze and tail suspension). Body weight and food intake were assessed weekly. Visceral adiposity, the hippocampal and hypothalamic protein expression of BDNF, 5-HT1A (5-HT1A serotonin receptor) and TPH2 (key enzyme in serotonin synthesis), were evaluated after euthanasia. RESULTS: The dietary intervention involved changing from a HFD to a CD over an 8-week period, effectively reduced body weight gain, adiposity, and anhedonia-like behavior. In the OB + HFD group, we saw a lower sucrose preference and shorter traveled distance in the open field, along with increased pro-BDNF expression in the hypothalamus compared to the OB + CD mice. However, the levels of TPH2 and 5-HT1A remained unchanged. CONCLUSION: The HFD model induced both obesity and anhedonia, but the dietary intervention successfully improved these conditions.

Long-term calorie restriction prevented memory impairment in middle-aged male mice and increased a marker of DNA oxidative stress in hippocampal dentate gyrus.

Calorie restriction (CR) is a non-invasive and economic approachknown to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle-age. Hence, weaimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targetingΔFosB (neuronal activity), brain-derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle-age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety-type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety-type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol.

Purple Carrot Extract Exhibits a Neuroprotective Profile in th e Nigrostriatal Pathway in the Reserpine-induced Model of Parkinson 's Disease.

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Even with scientific and technological advances, the therapeutic approaches used for the treatment of PD have shown to be largely ineffective in controlling the progression of symptoms in the long term. There is a growing demand for the development of novel therapeutic strategies for PD treatment. Different herbs and supplements have been considered as adjuvant to treat the symptoms of Parkinsonism. The carrot is one of the most consumed vegetable species worldwide, and its root is known for its content of anthocyanins, which possess antioxidant and antiinflammatory properties. This study evaluated the neuroprotective effect of purple carrot extract (CAR) in rats on the reserpine (RES)-induced progressive parkinsonism model. METHODS: Male rats (6-month-old) received orally the CAR (400 mg/kg) or vehicle and subcutaneously RES (0.01 mg/kg) or vehicle for 28 days (Preventive Phase). From the 29th day, rats received CAR or vehicle daily and RES (0.1 mg/kg) or vehicle every other day (for 23 days, Protective phase). Behavioral tests were conducted throughout the treatment. Upon completion, the animals' brain were processed for tyrosine hydroxylase (TH) immunohistochemical assessment. RESULTS: Our results showed that the chronic treatment of CAR protected against motor disabilities, reducing the time of catalepsy behavior and decreasing the frequency of oral movements, possibly by preserving TH levels in the Ventral Tegmental Area (VTA) and SNpc. CONCLUSION: CAR extract is effective to attenuate motor symptoms in rats associated with increased TH+ levels in the Ventral Tegmental Area (VTA) and SNpc, indicating the potential nutraceutical benefits of CAR extract in a progressive parkinsonism model induced by RES.

Anti-inflammatory Effects of Compounds Extracted from Marine Sponge s: A Systematic Review.

BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.

Terpenes extracted from marine sponges with antioxidant activity: a systematic review.

Marine biodiversity has emerged as a very promising resource of bioactive compounds and secondary metabolites from different sea organisms. The sponge's secondary metabolites demonstrated various bioactivities and potential pharmacological properties. This systematic review of the literature focuses on the advances achieved in the antioxidant potential of marine sponges in vitro. The review was performed in accordance with PRISMA guidelines. The main inclusion criterion for analysis was articles with identification of compounds from terpene classes that demonstrate antioxidant activity in vitro. Searching in three different databases, two hundred articles were selected. After screening abstracts, titles and evaluating for eligibility of manuscripts 14 articles were included. The most performed analyzes to detect antioxidant activity were scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and measurement of intracellular reactive oxygen species (ROS). It was possible to identify 17 compounds of the terpene class with pronounced antioxidant activity in vitro. Scientific evidence of the studies included in this review was accessed by the GRADE analysis. Terpenes play an important ecological role, moreover these molecules have a pharmaceutical and industrial application.

Sakuranetin exerts anticonvulsant effect in bicuculline-induced seizures.

Epilepsy is a chronic neurological disorder characterized by an abnormal, spontaneous, and synchronized neuronal hyperactivity. Therapeutic approaches for controlling epileptic seizures are associated with pharmacoresistance and side effects burden. Previous studies reported that different natural products may have neuroprotector effects. Sakuranetin (SAK) is a flavanone with antiparasitic, anti-inflammatory, antimutagenic, antiallergic, and antioxidant activity. In the present work, the effect of SAK on seizures in a model of status epilepticus induced by bicuculline (BIC) in mice was evaluated. Male Swiss mice received an intracerebroventricular injection (i.c.v.) of SAK (1, 10, or 20 mg/kg-SAK1, SAK10, or SAK20). Firstly, animals were evaluated in the open field (OF; 20 min), afterwards in the elevated plus maze (EPM) test (5 min). Next, 30 min prior the administration of BIC (1 mg/kg), mice received an injection of SAK (1 or 10 mg/kg, i.c.v.) and were observed in the OF (20 min) for seizures assessment. After behavioral procedures, immunohistochemical analysis of c-Fos was performed. Our main results showed that the lowest doses of SAK (1 and 10 mg/kg) increased the total distance traveled in the OF, moreover protected against seizures and death on the BIC-induced seizures model. Furthermore, SAK treatment reduced neuronal activity on the dentate gyrus of the BIC-treated animals. Taken together, our results suggest an anticonvulsant effect of SAK, which could be used for the development of anticonvulsants based on natural products from herbal source.

Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models.

Asthma is a respiratory allergic disease presenting a high prevalence worldwide, and it is responsible for several complications throughout life, including death. Fortunately, asthma is no longer recognized as a unique manifestation but as a very heterogenic manifestation. Its phenotypes and endotypes are known, respectively, as pathologic and molecular features that might not be directly associated with each other. The increasing number of studies covering this issue has brought significant insights and knowledge that are constantly expanding. In this review, we intended to summarize this new information obtained from clinical studies, which not only allowed for the creation of patient clusters by means of personalized medicine and a deeper molecular evaluation, but also created a connection with data obtained from experimental models, especially murine models. We gathered information regarding sensitization and trigger and emphasizing the most relevant phenotypes and endotypes, such as Th2-high asthma and Th2-low asthma, which included smoking and obesity-related asthma and mixed and paucigranulocytic asthma, not only in physiopathology and the clinic but also in how these phenotypes can be determined with relative similarity using murine models. We also further investigated how clinical studies have been treating patients using newly developed drugs focusing on specific biomarkers that are more relevant according to the patient's clinical manifestation of the disease.

Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats.

Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.

Maternal high-fat diet increases anhedonic behavior and modulates hippocampal Mash1 and BDNF expression in adult offspring.

BACKGROUND: The consumption of a high-fat diet (HFD) during pregnancy and perinatal periods can lead to long-term effects in the offspring central nervous system, affecting pathways related to neurogenesis and behavior, and increasing predispositions to depressive and anxiety-like behaviors. Thus, this study aimed to investigate the effects of a maternal HFD on the hippocampi of adult offspring and behaviors related to anxiety and depression. METHODS: The protein and mRNA expression of the brain-derived neurotrophic factor (BDNF), Mash1, Notch1, Hes5, serotonin transporter (SERT), 5-HT1A serotonergic receptor (5-HT1A), tryptophan hydroxylase 2 (TPH2, key enzyme of serotonin synthesis), JNK and pJNK were analyzed in the hippocampi of male Swiss mice. Hippocampal serotonin levels were measured using ELISA. The lipid peroxidation, total oxidant status, total antioxidant status, and GSH/GSSG were evaluated as oxidative stress measures. For the behavioral analysis, the open field, elevated plus maze, and sucrose preference tests were used. RESULTS: Maternal HFD led to increased body weight in dams and their offspring, as well as altered body composition and LDL levels in the offspring. There were no alterations in oxidative stress or JNK phosphorylation. Hippocampal Mash1 and BDNF expression were altered in HFD offspring. The HFD offspring exhibited anhedonic behavior. CONCLUSION: These findings suggest that maternal HFD leads to long-term alterations in the offspring's neurotrophic systems, impairing their behavior.

Palatable high-fat diet intake influences mnemonic and emotional aspects in female rats in an estrous cycle-dependent manner.

Worldwide, the excessive consumption of fat and/or sugar has increased considerably. Palatable high-fat diets (HFDs) lead to metabolic disturbances and obesity, and impact emotional and cognitive processes. Previous studies in rodent models suggested that HFDs often cause multiple behavioral alterations, such as learning and memory deficits, and anxiety-like behaviors. Different sexes imply different behavioral and cognitive abilities; yet, most of these studies dealt with male or ovariectomized rats. We evaluated HFD effects in female rats submitted to different behavioral tasks, considering the effects of endogenous hormonal variations throughout estrous cycle. Female Wistar rats in each phase of the estrous cycle using commercial chow (CC) or HFD for 32 days. During treatment, behavioral assessments using sucrose preference (SP), elevated plus-maze (EPM), open field (OF) and novel-object recognition (NOR). At the end of the behavioral tests, animals were euthanized, and performed an immunohistochemical analysis of the brains by brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH). The main results demonstrated that (1) HFD-fed rats had higher body mass gain and food intake, without altering caloric intake, (2) rats in diestrus had lower sucrose intake, (3) females in metestrus and diestrus showed deficits in the novel-object recognition memory. Furthermore, TH-immunoreactivity decreased in the dorsal striatum and BDNF in the hippocampus in HFD-fed females. These results suggest that HFD alters neurochemical and metabolic aspects that may induce phase-dependent behavioral changes in female rats.

Myrtenol complexed with ß-cyclodextrin ameliorates behavioural deficits and reduces oxidative stress in the reserpine-induced animal model of Parkinsonism.

Current pharmacological approaches to treat Parkinson's disease have low long-term efficacy and important adverse side effects. The development of new pharmacological therapies has focused on novel plant-derived phytochemicals. The alcoholic monoterpene myrtenol has been isolated from several plant species, and has anxiolytic, analgesic, anti-inflammatory and antioxidant actions. Our study evaluated the neuroprotective potential of myrtenol complexed with ß-cyclodextrin (MYR) on a progressive parkinsonism model induced by reserpine (RES) in mice. The complexation with cyclodextrins enhances the pharmacological action of monoterpenes. Male Swiss mice were treated daily with MYR (5 mg/kg, p.o.) and with RES (0.1 mg/kg, s.c.) every other day during 28 days. Behavioural evaluations were conducted across treatment. At the end of the treatment, immunohistochemistry for tyrosine hydroxylase (TH) and oxidative stress parameters were evaluated. Chronic MYR-treatment protected against olfactory sensibility loss, restored short-term memory and decreased RES-induced motor impairments. Moreover, this treatment prevented dopaminergic depletion and reduced the oxidative status index in the dorsal striatum. Therefore, MYR ameliorated motor and non-motor impairments in the progressive animal model of parkinsonism, possibly by an antioxidant action. Additional research is needed to investigate the mechanisms involved in this neuroprotective effect.

Postnatal exposure to fluoxetine led to cognitive-emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats.

The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (~PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7-PND21)- or vehicle-treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety- and depression-like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short-term (but not long-term) recognition memory impairments, and reduced parvalbumin-positive interneurons in the hippocampus. In addition, the results revealed developmental sex-dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.

Characterization and Biological Performance of Marine Sponge Collagen

Abstract This study characterized the morphological aspects of marine collagen - spongin (SPG) extract from marine sponges, as well as, evaluating its in vitro and in vivo biological performance. Aplysina fulva marine sponge was used for the SPG extraction. It was investigated the physicochemical and morphological properties of SPG by using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and compared to PMMA and bovine collagen. Additionally, the SPG cytotoxicity and its influence on cell proliferation, through in vitro tests. Moreover, the in vivo biological response was investigated using an experimental model of tibial bone defect. The results demonstrated that SPG presented an irregular granular aspect, with a composition of OH, C=O, NH, CN and an amorphous profile. Also, in vitro viability results for the L929 and MC3T3 cell lines cultured with SPG extracts demonstrated normal growth in comparison to controls, except for MC3T3 viability at day 3. For in vivo analysis, using tibial bone defects in rats, SPG treated animals presented an increased rate of material resorption and higher granulation and bone formation deposition in the region of the defect, mainly after 45 days. As a conclusion, SPG was successfully extracted. The in vitro and in vivo studies pointed out that SPG samples produced an increase in L929 and MC3T3 viability and improved the performance in tibial bone defects. It can be concluded that SPG can be used as a bone graft for bone regeneration.

Characterization of ß-cyclodextrin/myrtenol complex and its protective effect against nociceptive behavior and cognitive impairment in a chronic musculoskeletal pain model.

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with ß-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into ß-cyclodextrin cavity. The interaction between myrtenol and ß-cyclodextrin was confirmed by molecular docking. Hence, the SC ß-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and ß-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the ß-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, ß-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.

Eplingiella fruticosa (Lamiaceae) essential oil complexed with ß-cyclodextrin improves its anti-hyperalgesic effect in a chronic widespread non-inflammatory muscle pain animal model.

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with ßCD (HypEO-ßCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, ß-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-ßCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-ßCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with ß-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Memory impairment induced by different types of prolonged stress is dependent on the phase of the estrous cycle in female rats.

A growing body of evidence demonstrates that estrogen and corticosterone (CORT) impact on cognition and emotion. On the one hand, ovarian hormones may have beneficial effects on several neurophysiological processes, including memory. On the other hand, chronic exposure to stressful conditions has negative effects on brain structures related to learning and memory. In the present study, we used the plus-maze discriminative avoidance task (PMDAT) to evaluate the influence of endogenous variations of sex hormones and exposure to different types of prolonged stressors on learning, memory, anxiety-like behavior and locomotion. Female Wistar rats were submitted to seven consecutive days of restraint stress (4 h/day), overcrowding (18 h/day) or social isolation (18 h/day) and tested in different phases of the estrous cycle. The main results showed that: (1) neither stress conditions nor estrous cycle modified PMDAT acquisition; (2) restraint stress and social isolation induced memory impairments; (3) this impairment was observed particularly in females in metestrus/diestrus; (4) stressed females in estrus displayed less risk assessment behavior, suggesting reduced anxiety-like behavior; (5) restraint stress and social isolation, but not overcrowding, elevated corticosterone levels. Taken together, our findings suggest that the phase of the estrous cycle is an important modulatory factor of the cognitive processing disrupted by stress in female rats. Negative effects were observed in metestrus/diestrus, indicating that the peak of sex hormones may protect females against stress-induced memory impairment.

Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson's Disease.

Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson's disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

CA1 inactivation impairs episodic-like memory in rats.

Episodic memory was initially believed to be unique to humans. However, studies demonstrate that nonhuman species discriminate items based on the triad what, where and when. Here we addressed the role of the dorsal hippocampal subfield CA1 in an integrative what-where-when task in Wistar rats. We performed bilateral inactivation of dorsal CA1 with the GABAA agonist muscimol previously to the task. As expected, sham-operated animals recollected an integrative memory for objects (what), their places (where) and temporal order (when). However, the inactivation of CA1 impaired the performance of the three components of episodic-like memory. In addition, total time of objects exploration and distance traveled were not different between groups, indicating that rats had similar levels of motivation, thus, alterations in exploration does not account for impaired locomotor performance. Altogether, our data provides evidence that CA1 plays an important role in episodic-like memory.

Cerebellar Insulin/IGF-1 signaling in diabetic rats: Effects of exercise training.

The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32mg/kgb.w.). The training program consisted in swimming 5days/week, 1h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3ß, IRß and IGF-1R and the phosphorylation of ß-amyloid, Tau, ERK1+ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups; however, in TD, there was a reduction in hyperglycemia compared to SD. Diabetes increased Tau and ß-amyloid phosphorylation in both SD and TD groups. Furthermore, aerobic exercise increased ERK1+ERK2 expression in TC. The data showed that in cerebellum of diabetic rats induced by alloxan there are some proteins expression like Parkinson cerebellum increased, and the exercise training was not able to modulate the expression of these proteins.